Rikki Justin A.

Chu 12-C Paper Review on Loperamide March 15, 2019

Opiate receptor agonists such as morphine and opium have been used for centuries
for the treatment of diarrhea. Because of the popular side effects of these chemicals, other
means for treating diarrhea were developed. The most common and popular of these today is
loperamide, which is also an opioid agonist (Baker, 2007). Loperamide is an over-the-counter
drug that is used as an antimotility agent. Loperamide is sold under several brand names; the
most common of these that are found in the Philippines are under the brand name of Imodium
and Diatabs. Loperamide is generally used for the symptomatic relief of acute non-specific
diarrhea and chronic diarrhea associated with inflammatory bowel disease. In general, it works
by slowing down intestinal movement; thus, reducing water and fluid loss to the intestines and
improving stool consistency. According to Filer, Egan, & Nugent (2014), loperamide, or [N-
methyl-3H]loperamide, is synthesizd by the following process:
“An imine precursor was alkylated with [3H]methyl iodide to obtain a quaternary
intermediate, which was then reacted with 4-(4-chlorophenyl)-4-hydroxypiperidine to afford the
desired product [N-methyl-3H]loperamide”

As previously mentioned, loperamide is an opioid receptor agonist. It binds to the mu

opioid receptors in the myenteric plexus. The myenteric plexus is the the major nerve that
controls the motility of the gastrointestinal tract. Loperamide decreases the activity of the
myenteric plexus which in turn decreases the movement of the muscles of the intestinal wall,
thus slowing down peristalsis. This increases the amount of time substances stay in the
intestine, allowing for more water to be absorbed out of the fecal matter (Ooms, Degryse, &
Janssen, 1984).
The most common side effect associated with loperamide is constipation. Other
documented adverse reactions include cramps, nausea, dyspepsia, drowsiness, fatigue,
tiredness, headache, and dry mouth (Cunha, 2018). Most of these, however, pass by quickly.
Unlike other opioid agonists, loperamide does not have the ability to cross the blood-brain
barrier; thus, it has minimal effects towards the central nervous system. As such, loperamide
is considered free of abuse potential (Baker, 2007). Chronic use of loperamide in large doses
can permanently slow down peristalsis and predispose some people to megacolon, an
abnormal dilation of the colon. It is important to note that is cases of food poisoning,
loperamide should not be used as diarrhea in these cases is a mechanism of the body to expel
ingested toxicants.
 REFERENCES

Baker, D. E. (2007). Loperamide: a pharmacological review. Reviews in Gastroenterological

Disorders, 7, S11-8.
Cunha, J.P. (2018). Imodium side effects center. Retrieved from https://www.rxlist.com/imodiu
m-side-effects-drug-center.htm#overview
Filer, C. N., Egan, J. A., & Nugent, R. P. (2014). Synthesis and characterization of [N‐methyl
3H] loperamide. Journal of Labelled Compounds and Radiopharmaceuticals, 57(6),
437-439.
Ooms, L. A., Degryse, A. D., & Janssen, P. A. (1984). Mechanisms of action of
loperamide. Scandinavian journal of gastroenterology. Supplement, 96, 145-155.